Global WM Research Articles

Characterizing cerebral microhemorrhage associations in dementia subtypes in the UK Biobank

AbstractBackgroundCerebral microbleeds (CMBs) are associated with neurodegenerative diseases (Charidimou, 2011) and have been identified as an adverse amyloid‐related imaging abnormality event (ARIA‐H) related to amyloid clearing medications (Sperling, 2011). Identifying risk factors for CMBs can help refine inclusion criteria for clinical trials and mitigate the risk of ARIA‐H. CMBs are readily detected on T2*‐GRE MRI sequences, including susceptibility weighted imaging (SWI) – a modality used to detect magnetic field distortions caused by paramagnetic products like iron (Haacke, 2004, Liu, 2017). We explore CMB associations with demographic, disease, and imaging markers in a subset of participants with varying dementia subtypes and complaints in the UK Biobank (Miller, 2016).MethodA total of 75 participants who had clinically diagnosed or self‐reported dementia and SWI imaging were selected; 4 participants were excluded due to extreme motion. We used MARS criteria (Gregoire, 2009) to identify CMBs on SWI and validated our findings using other sequences to exclude CMB ‘mimics’ (Figure 1A). The number, classification, and position of CMBs were recorded. Logistic regressions modeling the outcome of at least one ‘definite’ or ‘total’ (‘definite’ + ‘possible’) CMB were performed and effect sizes were calculated across hippocampal volume, white matter hyperintensity load (WMH), and global WM diffusion MRI (dMRI) microstructural measures.ResultParticipants were predominantly male (65%) with a mean age of 69.8 (± 7.1) years. 9 participants had at least one ‘definite’ CMB and 8 more had at least one ‘possible’ CMB for a ‘total’ of 17 individuals with CMBs. Individuals with CMB(s) were significantly older than those without. CMBs were mostly ‘strictly lobar’ for both definite (78%) and total (71%) classifications (Table 1). The presence of CMBs were found across a spectrum of dementia diagnoses (Figure 1B). Microstructural dMRI measures including global WM FA, MD, and ISOVF were significantly associated with presence of total CMBs (q<0.05) (Figure 2).ConclusionMeasures reflecting WM organization were sensitive to the pathophysiology of CMBs in those with dementia. Future work should investigate whether WM microstructure can predict the development of CMBs in those with dementia, particularly in individuals undergoing amyloid clearing treatments.

White matter changes with cerebrovascular disease and Alzheimer’s disease pathologies

AbstractBackgroundWhite matter (WM) plays an important role in cognitive function and undergoes substantial changes due to aging and increase in AD and AD related dementia (AD/ADRD) pathologies. While recent work proposed measurement of global WM changes from diffusion MRI as biomarkers for Cerebrovascular disease (CVD) such as PSMD and free water, there needs to be a better understanding of WM changes due to AD/ADRD pathologies. The goal of our recent work was to understand white matter changes with CVD and AD – common pathologies in AD/ADRD ‐ utilizing data from Mayo Clinic Study of Aging and Mayo ADRC.MethodUsing diffusion MRI (dMRI) in 718 participants from Mayo Clinic Study of Aging (mean age = 71.1 years, 56% male), we investigated relationships between commonly used dMRI measures and vascular risk as well as global amyloid PET. In a subset of 233 participants who were amyloid‐PET positive and also competed Tau‐PET (flortaucipir) from Mayo Clinic Study of Aging and Mayo ADRC, we investigated associations between regional flortaucipir SUVRs in Braak stages and regional WM changes.ResultsWe found greater frontal lobe WM damage with increasing vascular risk across all dMRI measures. We previously validated the strong relationship between the genu of the corpus callosum (anterior interhemispheric connections) dMRI measurements made on antemortem scans and cerebrovascular pathology observed on postmortem tissue (Nguyen et. al. Acta Neuropathologica 2022) supporting the utility of genu of the corpus callosum dMRI measures as a potential CVD biomarker. Also, we found greater posterior WM damage with increasing amyloid burden. Among the 233 amyloid positive participants, we found spatially dependent WM degeneration associated with regional flortaucipir SUVRs in Braak stages with greater extent of posterior WM damage. Further, dMRI measurements of the WM damage provided complementary information about disease staging and progression of AD in addition to flortaucipir SUVR measurements.ConclusionsAnterior WM measurements may be more specific to CVD and posterior WM changes are seen with increasing AD pathological burden. Our results suggest that WM changes observed with CVD and typical AD may be different and have clinical utility for differential diagnosis and disease staging.

Neurite orientation dispersion and density imaging of white matter microstructure in sensory processing dysfunction with versus without comorbid ADHD.

Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined. The present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups. SPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum. We conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD.

Selective Motor Control is a Clinical Correlate of Brain Motor Tract Impairment in Children with Spastic Bilateral Cerebral Palsy.

Selective voluntary motor control is an important factor influencing gross motor function, interjoint coordination, and the outcome of hamstring-lengthening surgery in spastic cerebral palsy. Using DTI, we investigated whether selective voluntary motor control would show strong correlations with WM motor tract microstructure and whether selective voluntary motor control is more sensitive to global WM impairment than gross motor function. Children with spastic bilateral cerebral palsy born preterm and typically developing children were recruited. The Selective Control Assessment of the Lower Extremity (SCALE) and Gross Motor Function Measure (GMFM) were assessed in participants with cerebral palsy. Participants underwent brain MR imaging to collect DWI data. Tract-Based Spatial Statistics was used to analyze the WM for between-group differences and correlations with SCALE and GMFM. ROI analyses compared motor regions. Twelve children with cerebral palsy (mean age, 11.5 years) and 12 typically developing children (mean age, 10.3 years) participated. Altered DTI outcomes were found throughout the whole brain for the cerebral palsy group. SCALE, developed to evaluate selective voluntary motor control in cerebral palsy, showed significant positive correlations with fractional anisotropy in more WM voxels throughout the whole brain and for motor regions, including the corticospinal tract and corpus callosum, compared with GMFM. A significant negative correlation between radial diffusivity and SCALE, but not GMFM, was found within the corpus callosum. SCALE was a more sensitive clinical correlate of motor and whole-brain WM tract impairment in children with spastic bilateral cerebral palsy, suggesting greater anisotropy and myelination in these regions for those with higher selective voluntary motor control.

Microstructural Tissue Changes in Alzheimer Disease Brains: Insights from Magnetization Transfer Imaging.

Reductions in magnetization transfer ratio have been associated with brain microstructural damage. We aim to compare magnetization transfer ratio in global and regional GM and WM between individuals with Alzheimer disease and healthy control participants to analyze the relationship between magnetization transfer ratio and cognitive functioning in Alzheimer disease. In this prospective study, participants with Alzheimer disease and a group of age-matched healthy control participants underwent clinical examinations and 3T MR imaging. Magnetization transfer ratios were determined in the cortex, AD-signature regions, normal-appearing WM, and WM hyperintensities. Seventy-seven study participants (mean age ± SD, 72 ± 8 years; 47 female) and 77 age-matched healthy control participants (mean age ± SD, 72 ± 8 years; 44 female) were evaluated. Magnetization transfer ratio values were lower in patients with Alzheimer disease than in healthy control participants in all investigated regions. When adjusting for atrophy and extent of WM hyperintensities, significant differences were seen in the global cortex (OR = 0.47; 95% CI: 0.22, 0.97; P = .04), in Alzheimer disease-signature regions (OR = 0.31; 95% CI: 0.14, 0.67; P = .003), in normal-appearing WM (OR = 0.59; 95% CI: 0.39, 0.88; P = .01), and in WM hyperintensities (OR = 0.18; 95% CI: 0.09, 0.33; P ≤ .001). The magnetization transfer ratio in these regions was an independent determinant of AD. When correcting for atrophy and WM hyperintensity extent, lower GM magnetization transfer ratios were associated with poorer global cognition, language function, and constructional praxis. Alzheimer disease is associated with magnetization transfer ratio reductions in GM and WM regions of the brain. Lower magnetization transfer ratios in the entire cortex and AD-signature regions contribute to cognitive impairment independent of brain atrophy and WM damage.

Increasing body mass index in an elderly cohort: Effects on the quantitative MR parameters of the brain.

Body mass index (BMI) is increasing in a large number of elderly persons. This increase in BMI is known to put one at risk for many "diseases of aging," although less is known about how a change in BMI may affect the brains of the elderly. To investigate the relationship between BMI and quantitative water content, T1 , T2 *, and the semi-quantitative magnetization transfer ratio (MTR) of various structures in elderly brains. Cross-sectional. Forty-two adults (BMI range: 19.1-33.5 kg/m2 , age range: 58-80 years). 3T MRI (two multi-echo gradient echoes, actual flip angle imaging, magnetization prepared rapid gradient echo, fluid attenuated inversion recovery). The 3D two-point method was used to derive (semi-)quantitative parameters in global white (WM) and gray matter (GM) and their regions as defined by the Johns Hopkins University and the Montreal Neurological Institute atlases. Multivariate linear regression with BMI as principal regressor, corrected for the additional regressors age, gender, and glycated hemoglobin. Spearman correlation between quantitative parameters of the regions showing significant changes and the lipid spectra / C-reactive protein (CRP). Voxel-based morphometry and analysis of covariance (ANCOVA) to explore changes in the GM volume. T1 increased significantly (P < 0.05) in the frontal, temporal, and parietal cortices, while the bilateral corona radiata, right superior longitudinal fasciculus, as well as the corpus callosum showed significant changes in the WM regions. T2 * increased significantly in the global WM and left corona radiata. Changes in MTR and the free water content did not reach significance. No significant correlation between any quantitative parameter and the lipid spectra or CRP could be identified. These results suggest that an elevated BMI predominantly affects T1 in WM as well as GM structures in the elderly human brain. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:514-523.

Connectivity and morphology of hubs of the cerebral structural connectome are associated with brain resilience in AD- and age-related pathology.

The physiological basis of resilience to age-associated and AD-typical neurodegenerative pathology is still not well understood. So far, the established resilience factor intelligence has been shown to be associated with white matter network global efficiency, a key constituent of which are highly connected hubs. However, hub properties have also been shown to be impaired in AD. Individual predisposition or vulnerability of hub properties may thus modulate the impact of pathology on cognitive outcome and form part of the physiological basis of resilience. 85 cognitively normal elderly subjects and patients with MCI with DWI, MRI and AV45-PET scans were included from ADNI. We reconstructed the global WM networks in each subject and characterized hub-properties of GM regions using graph theory by calculating regional betweenness centrality. Subsequently, we investigated whether regional GM volume (GMV) and structural WM connectivity (WMC) of more hub-like regions was more associated with resilience, quantified as cognitive performance independent of amyloid burden, tau and WM lesions. Subjects with higher resilience showed higher increased regional GMV and WMC in more hub-like compared to less hub-like GM-regions. Additionally, this association was in some instances further increased at elevated amounts of brain pathology. Higher GMV and WMC of more hub-like regions may contribute more to resilience compared to less hub-like regions, reflecting their increased importance to brain network efficiency, and may thus form part of the neurophysiological basis of resilience. Future studies should investigate the factors leading to higher GMV and WMC of hubs in non-demented elderly with higher resilience.

Longitudinal White Matter Changes following Carbon Monoxide Poisoning: A 9-Month Follow-Up Voxelwise Diffusional Kurtosis Imaging Study.

Patients with carbon monoxide (CO) intoxication exhibit progressive WM changes that are not well-understood. The purpose of this study was to detect longitudinal WM changes using voxelwise diffusional kurtosis imaging in patients with CO intoxication from the acute-to-chronic stage after CO intoxication. Twenty-four patients with CO intoxication and 21 age- and sex-matched healthy controls were enrolled in this study. Diffusional kurtosis imaging was performed on all subjects and was conducted repeatedly in patients at 1 week and 1, 3, and 9 months after CO intoxication. Voxelwise diffusional kurtosis imaging analysis was performed to detect global WM changes in the patients with and without WM lesions. Receiver operating characteristic analysis was performed to compare the performance of diffusional indices in differentiating patients with delayed neuropsychiatric sequelae from patients without them. In voxelwise analysis, progressive WM changes were detected in patients with WM lesions. In the acute phase, WM injuries were found mainly in the dopaminergic pathways at 1 week, whereas in the chronic stage, WM injuries extended toward subcortical areas from 1 to 9 months. However, no significant WM change was noted in patients without WM lesions during the 9 months after CO intoxication. Moreover, receiver operating characteristic analysis demonstrated that axial kurtosis and mean kurtosis values had better performance than other diffusional indices in differentiating patients with delayed neuropsychiatric sequelae from patients without them at 1 week after CO intoxication. Voxelwise diffusional kurtosis imaging analysis was helpful to longitudinally investigate WM changes and predict the prognosis of patients after CO intoxication.

Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study.

Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes. Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models. Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (P < .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures (P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (P ≤ .01), coupled with thalamic susceptibility changes (P = .05). Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

Evaluation of Normal-Appearing White Matter in Multiple Sclerosis Using Direct Visualization of Short Transverse Relaxation Time Component (ViSTa) Myelin Water Imaging and Gradient Echo and Spin Echo (GRASE) Myelin Water Imaging.

In multiple sclerosis (MS), not only lesions but also normal MRI-appearing white matter (NAWM) may undergo demyelination. To demonstrate the detection of NAWM demyelination using direct visualization of short transverse relaxation time component myelin water imaging (ViSTa-MWI) and to compare the results with those of conventional gradient echo and spin echo (GRASE)-MWI. Control/cohort. Twenty-five MS patients and 18 healthy controls (HC). 3T/ViSTa and GRASE-MWI. Using ViSTa and GRASE-MWI, myelin water fraction (MWF) of NAWM or normal WM was compared between MS (all patients or early-stage MS patients) and HC. The comparison was performed for a global WM mask and five regional WM masks. A general linear model was applied for the comparison. A statistical power and a minimum sample size for the significant difference were obtained. Spearman's correlation coefficient was calculated between MWF and clinical measures and between ViSTa-MWF and GRASE-MWF for the global WM mask. MWFs of ViSTa were significantly lower in the MS patients than those in the HC in all masks (P < 0.001). GRASE-MWI results revealed reduced MWFs only in global WM, genu, and optic radiation. ViSTa-MWI had higher statistical powers than that of GRASE-MWI (power: ViSTa = 99.2 ± 1.6% and GRASE = 75.5 ± 31.0%; sample size: ViSTa = 18 ± 9 and GRASE = 78 ± 75). In early-stage MS, MWFs of ViSTa were significantly lower than those of the HC in all masks except for centrum semiovale; however, MWFs of GRASE MWI were significantly lower only in optic radiation. Disease duration was correlated with both MWIs (ViSTa; r = -0.437 and GRASE; r = -0.445). ViSTa and GRASE MWFs were significantly correlated in the HC (r = 0.664) and MS (r = 0.768). ViSTa-MWI may detect a reduction of MWF in NAWM of MS. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1091-1098.

Spatial Correlation of Pathology and Perfusion Changes within the Cortex and White Matter in Multiple Sclerosis.

The spatial correlation between WM and cortical GM disease in multiple sclerosis is controversial and has not been previously assessed with perfusion MR imaging. We sought to determine the nature of association between lobar WM, cortical GM, volume and perfusion. Nineteen individuals with secondary-progressive multiple sclerosis, 19 with relapsing-remitting multiple sclerosis, and 19 age-matched healthy controls were recruited. Quantitative MR perfusion imaging was used to derive CBF, CBV, and MTT within cortical GM, WM, and T2-hyperintense lesions. A 2-step multivariate linear regression (corrected for age, disease duration, and Expanded Disability Status Scale) was used to assess correlations between perfusion and volume measures in global and lobar normal-appearing WM, cortical GM, and T2-hyperintense lesions. The Bonferroni adjustment was applied as appropriate. Global cortical GM and WM volume was significantly reduced for each group comparison, except cortical GM volume of those with relapsing-remitting multiple sclerosis versus controls. Global and lobar cortical GM CBF and CBV were reduced in secondary-progressive multiple sclerosis compared with other groups but not for relapsing-remitting multiple sclerosis versus controls. Global and lobar WM CBF and CBV were not significantly different across groups. The distribution of lobar cortical GM and WM volume reduction was disparate, except for the occipital lobes in patients with secondary-progressive multiple sclerosis versus those with relapsing-remitting multiple sclerosis. Moderate associations were identified between lobar cortical GM and lobar normal-appearing WM volume in controls and in the left temporal lobe in relapsing-remitting multiple sclerosis. No significant associations occurred between cortical GM and WM perfusion or volume. Strong correlations were observed between cortical-GM perfusion, normal appearing WM and lesional perfusion, with respect to each global and lobar region within HC, and RRMS and SPMS patients (R2 ≤ 0.96, P < .006 and R2 ≤ 0.738, P < .006). The weak correlation between lobar WM and cortical GM volume loss and perfusion reduction suggests the independent pathophysiology of WM and cortical GM disease.

Extensive white matter dysfunction in cognitively impaired patients with secondary-progressive multiple sclerosis.

Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (p(corr) < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (p(corr) > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.

Impact of a Single Bout of Aerobic Exercise on Regional Brain Perfusion and Activation Responses in Healthy Young Adults

PurposeDespite the generally accepted view that aerobic exercise can have positive effects on brain health, few studies have measured brain responses to exercise over a short time span. The purpose of this study was to examine the impact within one hour of a single bout of exercise on brain perfusion and neuronal activation.MethodsHealthy adults (n = 16; age range: 20–35 yrs) were scanned using Magnetic Resonance Imaging (MRI) before and after 20 minutes of exercise at 70% of their age-predicted maximal heart rate. Pseudo-continuous arterial spin labeling (pcASL) was used to measure absolute cerebral blood flow (CBF) prior to exercise (pre) and at 10 min (post-10) and 40 min (post-40) post-exercise. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) was performed pre and post-exercise to characterize activation differences related to a go/no-go reaction time task.ResultsCompared to pre-exercise levels, grey matter CBF was 11% (±9%) lower at post-10 (P<0.0004) and not different at post-40 (P = 0.12), while global WM CBF was increased at both time points post-exercise (P<0.0006). Regionally, the hippocampus and insula showed a decrease in perfusion in ROI-analysis at post-10 (P<0.005, FDR corrected), whereas voxel-wise analysis identified elevated perfusion in the left medial postcentral gyrus at post-40 compared to pre (pcorrected = 0.05). BOLD activations were consistent between sessions, however, the left parietal operculum showed reduced BOLD activation after exercise.ConclusionThis study provides preliminary evidence of regionalized brain effects associated with a single bout of aerobic exercise. The observed acute cerebrovascular responses may provide some insight into the brain’s ability to change in relation to chronic interventions.

Proton MR spectroscopy correlates diffuse axonal abnormalities with post-concussive symptoms in mild traumatic brain injury.

There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal abnormalities quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (¹H-MRSI) correlated with patients' PCS, we retrospectively studied 26 mTBI patients (mean Glasgow Coma Scale [GCS] score of 14.7), 18- to 56-year-olds and 13 controls three to 55 days post-injury. All were scanned at 3 Tesla with T1- and T2-weighted MRI and 3D ¹H-MRSI (480 voxels over 360 cm³, ∼30% of the brain). On scan day, patients completed a symptom questionnaire, and those who indicated at least one of the most common subacute mTBI symptoms (headache, dizziness, sleep disturbance, memory deficits, blurred vision) were grouped as PCS-positive. Global gray matter and white matter (GM/WM) absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) in PCS-positive and PCS-negative patients were compared to age- and gender-matched controls using two-way analysis of variance. The results showed that the PCS-negative group (n=11) and controls (n=8) did not differ in any GM or WM metabolite level. The PCS-positive patients (n=15) had lower WM NAA than the controls (n=12; 7.0 ± 0.6 versus 7.9 ± 0.5mM; p=0.0007). Global WM NAA, therefore, showed sensitivity to the TBI sequelae associated with common PCS in patients with mostly normal neuroimaging, as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.

Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8‐depleted rhesus macaques: proton MRS imaging at 3 T

To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 × 16 × 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm(3) spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 ± 0.4 to 6.0 ± 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 ± 0.2 to 1.0 ± 0.1 mM (p < 0.003); global mI increased 11%: 5.7 ± 0.4 to 6.5 ± 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response.

Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study.

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging ((1)H-MRSI). T1- and T2-weighted MRI images and three-dimensional (1)H-MRSI (480 voxels over 360 cm(3), about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18-56 years old, 3-55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This (1)H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.

White matter abnormalities correlate with neurocognitive performance in patients with HBV-related cirrhosis

BackgroundWhite matter (WM) abnormalities are common in cirrhotic patients and possibly contribute to hepatic encephalopathy (HE), a frequent neuropsychiatric complication of cirrhosis. However, little is known about these WM abnormalities and their relationship to neurocognitive deficits in patients with HBV-related cirrhosis. MethodsThree-dimensional T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) scans were obtained from 67 patients with HBV-related cirrhosis and 40 controls. Voxel-based morphometry and voxel-based DTI were performed to detect macroscopic atrophy and damage to the microstructural integrity of the WM, respectively. Correlation analyses were performed to investigate the relationships between WM abnormalities and neurocognitive performances. ResultsPatients with cirrhosis exhibited significantly decreased WM volume and fractional anisotropy (FA) values, especially in the corpus callosum, thalamus, extra-nuclear area, sensorimotor area, fusiform gyrus, lingual gyrus, and frontal lobes. These abnormalities were more severe with increasing Child–Pugh stage, minimal HE, and previous overt HE. Changes in the corpus callosum, frontal lobe, sensorimotor area, internal capsule, and temporal–occipital lobes were correlated with poor neurocognitive performance. Also, the significantly decreased global WM volume and mean FA value were correlated with poor neurocognitive performances. ConclusionsDiffuse WM abnormalities are common in patients with HBV-related cirrhosis. Advanced liver disease and episodes of HE are two factors associated with WM abnormalities. The correlation between poor neurocognitive performance and WM abnormalities suggests that WM abnormalities may be one of mechanisms underlying neurocognitive deficits in patients with HBV-related cirrhosis.

White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM.

A pilot study exploring the contribution of working memory to “jumping to conclusions” in people with first episode psychosis

Introduction. People with delusional beliefs “jump to conclusions” (JTC). This finding is well replicated. However, there is only limited exploration of the factors that might lead a person to JTC. The aim of the present study was to explore the contribution of working memory processes (WM) and IQ to hasty decision making and to investigate the stability of this bias over time. Methods. A single group cross-sectional design was utilised. The study was conducted in 2 phases: (1) an initial screening phase and (2) an experimental phase whereby we explored and tested hypotheses regarding the cognitive origins of the JTC bias. In Study 1, participants completed the beads task as well as measures of mood and symptoms. In Study 2, the same participants repeated the beads task, and completed a battery of neuropsychological tests designed to assess different facets of WM and IQ. Results. In most cases, “jumpers” were indistinguishable from “nonjumpers” in terms of their neuropsychological profiles. The only exception to this pattern was for visual working memory, in which “jumpers” performed better than “nonjumpers”. In terms of the temporal stability of the JTC bias, 8 individuals (out of the 29) effectively switched from being “jumpers” at T1 to “nonjumpers” at T2. Conclusions. This study casts doubt on reduced global WM as an explanation of JTC. Rather it may be that the differences in reasoning are related to the manipulation of visual material and do not extend to other areas of neuropsychological functioning. However, as our sample is small it may be underpowered to detect important differences. Future work is therefore needed to replicate these findings.